Acquired immune deficiency syndrome (AIDS) is characterized by immune suppression secondary to helper T cell depletion and a high incidence of various malignancies, including Kaposi's sarcoma, B cell lymphomas, and non-Hodgkin's lymphomas. We plan to study the molecular mechanisms of T lymphocyte killing in AIDS using a transient assay in which the specific role of the HTLV-III envelope in syncytium formation and cytopathicity can be dissected. We will examine the contribution of envelope- mediated events to the overall cytotoxicity of HTLV-III infection for T lymphocytes. We will attempt to define envelope domains important for host cell binding and for cell membrane fusion. In addition, host cell molecules that interact with the HTLV-III envelope to form syncytia will be studied. These structure- function studies of the HTLV-III envelope should provide insight into mechanisms of host cell entry by RNA tumor viruses. Furthermore, studies of HTLV-III envelope-mediated cytotoxicity will provide models for investigation of mechanisms of pathogenesis by animal and human leukemia viruses known to cause immunosuppressive disorders in addition to malignancies.